Genes involved in the determination and differentiation of adult tissues in Drosophila melanogaster have been identified by genetic interactions with homeotic and segmentation genes already known to be required in these tissues. Many new genes required for transcriptional activation or repression of developmental genes have been identified. In addition, we have begun to characterize the cis- acting sequences required for repression of one of the homeotic genes, the Sex combs reduced gene of the Antennapedia complex in order to understand the molecular mechanisms underlying homeotic gene repression and activation. Certain classes of chromosome rearrangements in the Antennapedia complex cause activation of the repressed wild-type gene on the non-rearranged chromosome. We have used these observations to formulate a model for homeotic gene repression requiring the interaction of multiple silencing elements within the homeotic genes, and have begun characterizing an artificial silencing element based on these predictions. We have also identified a new gene required for the functioning of these silencing elements, which may encode a hunchback-interacting protein involved in the switch from the initiation phase to the maintenance phase of silencing. One of the genes that we identified as a transcriptional activator of the homeotic genes, the brahma gene, encodes a large nuclear protein conserved from yeast to man. brahma mutations have in turn been used to identify other interacting genes required for transcriptional activation. We have characterized three of these brahma-interacting genes in more detail. All three show strong genetic interactions with brahma mutations and with each other. Two have been transposon-tagged for molecular analysis. We have also shown that the moira gene encodes a transcriptional activator of homeotic genes, but does not appear to be part of the brahma group of interacting genes.